A chemical messenger in the nervous system

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Neurotransmitters are often referred to as the body’s chemical messengers. They are the molecules used by the nervous system to transmit messages between neurons, or from neurons to muscles.

Communication between two neurons happens in the synaptic cleft (the small gap between the synapses of neurons). Here, electrical signals that have travelled along the axon are briefly converted into chemical ones through the release of neurotransmitters, causing a specific response in the receiving neuron.

A neurotransmitter influences a neuron in one of three ways: excitatory, inhibitory or modulatory.

An excitatory transmitter promotes the generation of an electrical signal called an action potential in the receiving neuron, while an inhibitory transmitter prevents it. Whether a neurotransmitter is excitatory or inhibitory depends on the receptor it binds to.

Neuromodulators are a bit different, as they are not restricted to the synaptic cleft between two neurons, and so can affect large numbers of neurons at once. Neuromodulators therefore regulate populations of neurons, while also operating over a slower time course than excitatory and inhibitory transmitters.

Most neurotransmitters are either small amine molecules, amino acids, or neuropeptides. There are about a dozen known small-molecule neurotransmitters and more than 100 different neuropeptides, and neuroscientists are still discovering more about these chemical messengers. These chemicals and their interactions are involved in countless functions of the nervous system as well as controlling bodily functions.

The first neurotransmitter to be discovered was a small molecule called acetylcholine. It plays a major role in the peripheral nervous system, where it is released by motor neurons and neurons of the autonomic nervous system. It also plays an important role in the central nervous system in maintaining cognitive function. Damage to the cholinergic neurons of the CNS is associated with Alzheimer disease.

Glutamate is the primary excitatory transmitter in the central nervous system. Conversely, a major inhibitory transmitter is its derivative γ-aminobutyric acid (GABA), while another inhibitory neurotransmitter is the amino acid called glycine, which is mainly found in the spinal cord.

Many neuromodulators, such as dopamine, are monoamines. There are several dopamine pathways in the brain, and this neurotransmitter is involved in many functions, including motor control, reward and reinforcement, and motivation.

Noradrenaline (or norepinephrine) is another monoamine, and is the primary neurotransmitter in the sympathetic nervous system where it works on the activity of various organs in the body to control blood pressure, heart rate, liver function and many other functions.

Neurons that use serotonin (another monoamine) project to various parts of the nervous system. As a result, serotonin is involved in functions such as sleep, memory, appetite, mood and others. It is also produced in the gastrointestinal tract in response to food.

Histamine, the last of the major monoamines, plays a role in metabolism, temperature control, regulating various hormones, and controlling the sleep-wake cycle, amongst other functions.

The autonomic nervous system works by way of chemical messengers. There’re different chemical messengers and one of the more important families of chemical messengers is catecholamines.  This is an area that has been of interest to me for many years.  The catecholamines are key chemical messengers both in the brain and in all the organs of the body.

It’s important to realize that a key aspect of autonomic function is neurotransmission.  Chemical messengers are released from nerves and have key effects.  The general arrangement is shown here.  In response to nerve traffic there’s release of a transmitter that’s being stored in bubble-like spheres called vesicles, and the chemical messenger reaches the target organ and causes cellular activity.  Because of the changes, like just say in blood pressure and so forth, there’s afferent traffic to the brain which affects the efferent traffic and so you have this cycle and it’s a negative feedback loop.  Negative feedback just means here is a positive effect, here is a negative effect and any time you’ve got a cycle like this where there’s an odd number of negative signs, that’s a negative feedback loop, the level of the monitored variable, let us just say blood pressure, is going to be held stable.  Negative feedback loop. 

Norepinephrine, which is the key chemical messenger neurotransmitter of the sympathetic noradrenergic system, is made in vesicles.  It’s made inside the vesicles in the sympathetic nerve terminals.  I guess she already knows everything And a key enzyme is dopamine beta hydroxylase or DBH.  There are rare patients who have a lack of dopamine beta hydroxylase.  Because of that, the person can’t make norepinephrine.  Because of that there are all sorts of effects on that part of the autonomic nervous system but here is a quiz question for you.  If you had a patient with DBH deficiency, would that patient be able to sweat?  Yes, because you don’t need norepinephrine to sweat.  That was the sympathetic cholinergic system to a large extent.  So, acetylcholine is a chemical messenger there.  It’s not quite that simple but the fact of the matter is that people with DBH deficiency do sweat. Here is a beautiful image provided by Risa Isonaka showing either vesicles or clusters of vesicles (we haven’t figured that out) in human sympathetic neuron.  This is inside the ganglion. 

Exocytosis is important, so I just want to go over how the chemical messenger gets out.  The chemical messenger gets out because the vesicle physically, physically goes to the membrane surface and then pourates, right here, and then the soluble contents come out.  That’s how chemical neurotransmission happens.  So, if you look under an electron microscope, you can actually see these little omega signs, it means the pourated vesicles that are fused with the membrane surface, but the vast majority of vesicles are not pourated, only a teeny amount of the storage transmitter is released under normal circumstances. 

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